12The cerebral cortex underlies our complex cognitive capabilities, yet we know little about the specific genetic loci influencing human cortical structure. To identify genetic variants, including structural variants, impacting cortical structure, we conducted a genome-wide association meta-analysis of brain MRI data from 51,662 individuals. We analysed the surface area and average thickness of the whole cortex and 34 regions with known functional specialisations. We identified 255 nominally significant loci (P ≤ 5 x 10 -8 ); 199 survived multiple testing correction (P ≤ 8.3 x 10 -10 ; 187 surface area; 12 thickness). We found significant enrichment for loci influencing total surface area within regulatory elements active during prenatal cortical development, supporting the radial unit hypothesis. Loci impacting regional surface area cluster near genes in Wnt signalling pathways, known to influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression and ADHD.One Sentence Summary: Common genetic variation is associated with inter-individual variation in the structure of the human cortex, both globally and within specific regions, and is shared with genetic risk factors for some neuropsychiatric disorders.The human cerebral cortex is the outer grey matter layer of the brain, which is implicated in multiple aspects of higher cognitive function. Its distinct folding pattern is characterised by convex (gyral) and concave (sulcal) regions. Computational brain mapping approaches use the consistent folding patterns across individual cortices to label brain regions(1). During fetal development excitatory neurons, the predominant neuronal cell-type in the cortex, are generated from neural progenitor cells in the developing germinal zone(2). The radial unit hypothesis(3) posits that the expansion of cortical surface area (SA) is driven by the proliferation of these neural progenitor cells, whereas thickness (TH) is determined by the number of neurogenic divisions. Variation in global and regional measures of cortical SA and TH are associated with neuropsychiatric disorders and psychological traits(4) ( Table S1). Twin and family-based brain imaging studies show that SA and TH measurements are highly heritable and are largely influenced by independent genetic factors(5). Despite extensive studies of genes impacting cortical structure in model organisms (6), our current understanding of genetic variation impacting human cortical size and patterning is limited to rare, highly penetrant variants (7,8). These variants often disrupt cortical development, leading to altered post-natal structure. However, little is known about how common genetic variants impact human cortical SA and TH.To address this, we conducted genome-wide association meta-analyses of cortical SA and TH measures in 51,662 individuals from 60 cohorts from around the world (Tables S2-S4). Cortical measures were extracted from structural brain MRI scan...

Available treatment methods have shown little effect on the burden associated with mental health disorders. We review promising universal, selective, and indicated preventive mental health strategies that might reduce the incidence of mental health disorders, or shift expected trajectories to less debilitating outcomes. Some of these interventions also seem to be cost-effective. In the transition to mental illness, the cumulative lifetime effect of multiple small effect size risk factors progressively increases vulnerability to mental health disorders. This process might inform different levels and stages of tailored interventions to lessen risk, or increase protective factors and resilience, especially during sensitive developmental periods. Gaps between knowledge, policy, and practice need to be bridged. Future steps should emphasise mental health promotion, and improvement of early detection and interventions in clinical settings, schools, and the community, with essential support from society and policy makers.

Auditory verbal hallucinations (AVH) are complex experiences that occur in the context of various clinical disorders. AVH also occur in individuals from the general population who have no identifiable psychiatric or neurological diagnoses. This article reviews research on AVH in nonclinical individuals and provides a cross-disciplinary view of the clinical relevance of these experiences in defining the risk of mental illness and need for care. Prevalence rates of AVH vary according to measurement tool and indicate a continuum of experience in the general population. Cross-sectional comparisons of individuals with AVH with and without need for care reveal similarities in phenomenology and some underlying mechanisms but also highlight key differences in emotional valence of AVH, appraisals, and behavioral response. Longitudinal studies suggest that AVH are an antecedent of clinical disorders when combined with negative emotional states, specific cognitive difficulties and poor coping, plus family history of psychosis, and environmental exposures such as childhood adversity. However, their predictive value for specific psychiatric disorders is not entirely clear. The theoretical and clinical implications of the reviewed findings are discussed, together with directions for future research.

Conclusion:The results of aspirin addition to antipsychotic treatment seem promising, as does the addition of NAC and estrogens. These 3 agents are all very broadly active substances, and it has to be investigated if the beneficial effects on symptom severity are indeed mediated by their anti-inflammatory aspects.

Epidemiological studies suggest that auditory verbal hallucinations (AVH) occur in approximately 10%-15% of the general population, of whom only a small proportion has a clinically relevant psychotic disorder. It is unclear whether these hallucinations occur as an isolated phenomenon or if AVH in nonclinical individuals are part of a more general susceptibility to schizophrenia. For this study, 103 healthy individuals with frequent AVH were compared with 60 controls matched for sex, age, and education. All participants were examined by a psychiatrist using standardized diagnostic interviews and questionnaires. The individuals with AVH did not have clinically defined delusions, disorganization, or negative or catatonic symptoms, nor did they meet criteria for cluster A personality disorder. However, their global level of functioning was lower than in the controls and there was a pronounced increase on all subclusters of the Schizotypal Personality Questionnaire (SPQ) and the Peters Delusion Inventory, indicating a general increased schizotypal and delusional tendency in the hallucinating subjects. History of childhood trauma and family history of axis I disorders were also more prevalent in these individuals. We showed that higher SPQ scores, lower education, and higher family loading for psychiatric disorders, but not presence of AVH, were associated with lower global functioning. Our data suggest that AVH in otherwise healthy individuals are not an isolated phenomenon but part of a general vulnerability for schizophrenia.

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Despite a growing interest in auditory verbal hallucinations (AVHs) in different clinical and nonclinical groups, the phenomenological characteristics of such experiences have not yet been reviewed and contrasted, limiting our understanding of these phenomena on multiple empirical, theoretical, and clinical levels. We look at some of the most prominent descriptive features of AVHs in schizophrenia (SZ). These are then examined in clinical conditions including substance abuse, Parkinson's disease, epilepsy, dementia, late-onset SZ, mood disorders, borderline personality disorder, hearing impairment, and dissociative disorders. The phenomenological changes linked to AVHs in prepsychotic stages are also outlined, together with a review of AVHs in healthy persons. A discussion of key issues and future research directions concludes the review.

The pathophysiology of auditory verbal hallucinations (AVH) is largely unknown. Several functional imaging studies have measured cerebral activation during these hallucinations, but sample sizes were relatively small (one to eight subjects) and findings inconsistent. In this study cerebral activation was measured using fMRI in 24 psychotic patients while they experienced AVH in the scanner and, in another session, while they silently generated words. All patients were right handed and diagnosed with schizophrenia, schizo-affective disorder or psychotic disorder not otherwise specified. Group analysis for AVH revealed activation in the right homologue of Broca's area, bilateral insula, bilateral supramarginal gyri and right superior temporal gyrus. Broca's area and left superior temporal gyrus were not activated. Group analysis for word generation in these patients yielded activation in Broca's and Wernicke's areas and to a lesser degree their right-sided homologues, bilateral insula and anterior cingulate gyri. Lateralization of activity during AVH was not correlated with language lateralization, but rather with the degree to which the content of the hallucinations had a negative emotional valence. The main difference between cerebral activity during AVH and activity during normal inner speech appears to be the lateralization. The predominant engagement of the right inferior frontal area during AVH may be related to the typical low semantic complexity and negative emotional content.